Cardioembolic Etiology Research Articles

Performance of questionnaires to predict sleep-disordered breathing in acute stroke patients.

Sleep-disordered breathing is common in stroke and may negatively affect its outcome. Screening for sleep-disordered breathing in this setting is of interest but poorly studied. We aimed to evaluate the performance of eight obstructive sleep apnea screening questionnaires to predict sleep-disordered breathing in acute stroke or transient ischaemic attack patients, and to assess the impact of stroke/transient ischaemic attack-specific factors on sleep-disordered breathing prediction. We analysed acute stroke/transient ischaemic attack patients (N = 195) from a prospective cohort ("Sleep Deficiency and Stroke Outcome study"). Assessments included anthropometrics, stroke-specific parameters, sleep history, an in-hospital respiratory polygraphy within the first week after stroke, and obstructive sleep apnea screening questionnaires (Berlin Questionnaire, Epworth Sleepiness Scale, STOP-BANG, NoSAS, Sleep Apnea Clinical Score, No-Apnea, Sleep Obstructive apnea score optimized for Stroke, SLEEP-IN). In a binary classification task for respiratory event index ≥ 15 per hr, we evaluated the performance of the above-mentioned questionnaires. We used logistic regression to identify predictors for sleep-disordered breathing in this cohort. The areas under the curve for respiratory event index ≥ 15 per hr were: Berlin Questionnaire 0.60; STOP-BANG 0.72; NoSAS 0.69; No-Apnea 0.69; Sleep Apnea Clinical Score 0.75; Epworth Sleepiness Scale 0.50; Sleep Obstructive apnea score optimized for Stroke 0.58; and SLEEP-IN 0.67. The No-Apnea had the lowest false omission rate (0.13), a sensitivity of 0.97 and a specificity of 0.12. In multiple logistic regression analysis (respiratory event index ≥ 15 per hr), age, neck circumference, National Institutes of Health Stroke Scale at admission, prior stroke, cardioembolic stroke aetiology and observed apneas were associated with sleep-disordered breathing. The logistic regression model performed similar (area under the curve 0.80) to Sleep Apnea Clinical Score (p = 0.402) and STOP-BANG (p = 0.127), but outperformed the other questionnaires. Neither existing questionnaires nor our statistical model are sufficient to accurately diagnose sleep-disordered breathing after stroke, thus requiring sleep study evaluation. The No-Apnea questionnaire may help to identify patients amenable to sleep testing.

Clinical outcomes of reperfusion therapy in patients with site-specific basilar artery occlusion

BackgroundDespite its low incidence, basilar artery occlusion (BAO) remains a major therapeutic challenge since severe disability and death occur in about 80% of patients. Specific site of BAO (proximal, middle,...

Family History of Stroke Is Associated with Large- and Small-Vessel Etiology: A Systematic Review and Meta-Analysis.

Several studies have investigated the association between family history of stroke (FHS) and stroke etiology, recurrence, or mortality; however, the results have been discrepant. We conducted a systematic review with meta-analysis to further evaluate the associations. We searched Scopus database using the term "family history" AND "stroke" up to December 2023 to identify observational studies and systematic reviews reporting both the prevalence of FHS and the rates of stroke etiology or recurrence or mortality. Case reports, series, and narrative reviews were excluded. We used odds ratio (OR) as a common measure of association and I2 to determine heterogeneity of effects across studies. We have identified 22 articles (130,999 patients, 53% female), which met the prespecified inclusion criteria. After pooling the results, FHS was associated with large-vessel (OR, 1.24, 95% CI [1.07-1.44]), as well as small-vessel (OR, 1.17, 95% CI [1.05-1.31]), but not cardioembolic stroke etiology (OR, 0.74, 95% CI [0.60-0.90]). There was no relationship between FHS and stroke recurrence (OR, 1.16, 96% CI [0.84-1.61]), nor mortality (0.94, 95% CI [0.63-1.41]). FHS is associated with large- and small-vessel stroke etiology, but not stroke recurrence or mortality. These findings might be useful to physicians caring for stroke patients in their everyday practice.

Clinical and Radiological Differences between Patients Diagnosed with Acute Ischemic Stroke and Chameleons at the Emergency Room: Insights from a Single-Center Observational Study.

Scarce data exist about clinical/radiological differences between acute ischemic strokes diagnosed in the emergency room (AISER) and stroke chameleons (SCs). We aimed at describing the differences observed in a comprehensive stroke center in Chile. Prospective observational study of patients with ischemic stroke syndromes admitted to the emergency room (ER) of Clínica Alemana between December 2014 and October 2023. 1,197 patients were included; of these 63 (5.2%, 95% CI: 4.1-6.6) were SC; these were younger (p < 0.001), less frequently hypertensive (p = 0.03), and they also had lower systolic (SBP) (p < 0.001), diastolic blood pressures (DBP) (p = 0.011), and NIHSS (p < 0.001). Clinically, they presented less frequently gaze (p = 0.008) and campimetry alterations (p = 0.03), facial (p < 0.001) and limb weakness (left arm [p = 0.004], right arm (p = 0.041), left leg (p = 0.001), right leg p = 0.0029), sensory abnormalities (p < 0.001), and dysarthria (p < 0.001). Neuroradiological evaluations included less frequently large vessel occlusions (p = 0.01) and other stroke locations (p = 0.005); they also differed in their etiologies (p < 0.001). Brainstem strokes (p < 0.001) and extinction/inattention symptoms (p < 0.001) were only seen in AISER. In multivariate analysis, younger age (OR: 0.945; 95% CI: 0.93-0.96), DBP (OR: 0.97; 95% CI, 0.95-0.99), facial weakness (OR: 0.39; 95% CI: 0.19-0.78), sensory abnormities (OR: 0.16.18; 95% CI, 0.05-0.4), infratentorial location (OR: 0.36; 95% CI, 0.15-0.78), posterior circulation involvement (OR: 3.02; 95% CI, 1.45-6.3), cardioembolic (OR: 3.5; 95% CI, 1.56-7.99), and undetermined (OR: 2.42; 95% CI, 1.22-4.7; 95%) etiologies, remained statistically significant. A stepwise analysis including only clinical elements present on the patient's arrival to the ER, demonstrates that age (OR: 0.95; 95% CI: 0.94-0.97), DBP (OR: 0.97; 95% CI, 0.95-0.99), the presence of atrial fibrillation (OR: 2.22; 95% CI, 1.04-4.75, NIHSS (OR: 0.88; 95% CI, 0.71-0.89) and the presence in NIHSS of 1a level of consciousness (OR: 5.66; CI: 95% 1.8-16.9), 1b level of consciousness questions (OR: 3.023; 95% CI, 1.35-6.8), facial weakness (OR: 0.3; CI: 95% 0.17-0.8), and sensory abnormalities (OR: 0.27; 95% CI, 0.1-0.72) remained statistically significant. SC had clinical and radiological differences compared to AISER. An additional relevant finding is that neurological symptoms in a patient with atrial fibrillation, even with a negative diffusion-weighted imaging, should be carefully evaluated as a potential stroke until other causes are satisfactorily ruled out.

Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer. We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS. A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic. We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581.

Atrial imaging and cardiac Rhythm In cryptogenic Embolic Stroke: the ARIES study

Abstract Background One of the underlying causes of cryptogenic stroke is an unknown cardioembolic etiology, and the most frequent is atrial fibrillation (AF). It is not unusual to find non-sustained (<30 s) "microfibrillatory" atrial tachycardias (nsAT) or frequent atrial ectopic beats (AE) during the work-up but its pathological significance remains uncertain. Purpose Our aim is to analyze the risk of developing AF or nsAT in patients with cryptogenic stroke and compare their atrial function using advanced echocardiography and their clinical outcome during the follow-up. Methods The ARIES study (Atrial imaging and cardiac Rhythm In cryptogenic Embolic Stroke) is an observational, prospective study in patients admitted for recent cryptogenic stroke in a comprehensive Stroke Unit. We analyze the frequency of detecting AF and nsAT in two 30-day ECG records with a wearable device and we compare echocardiographic signs of left atrial (LA) dysfunction according to rhythm classification: AF, high-burden nsAT/AE (>2 nsAT/24 hours or >3.000 AE/24 hours respectively) and normal sinus rhythm (NSR). Finally, we evaluate stroke recurrence and mortality at 12-months and report changes in classification of stroke etiology during the follow-up. Results In total prolonged rhythm study (1st and 2nd 1-month wearable EKG), AF was found in 35 (32.1%) patients, high-burden nsAT/AE in 27 patients (24.8%) and normal rhythm was found in 47 patients (43.1%). Patients with AF compared with patients with NSR presented higher values in LA volume (69.9±21.8 vs 49.4±26.5, p<0.001) , LA index volume (38.8±11.2 vs 27.3±11.8 ml/m2, p<0.001), 3D LA index volume (50.6±17.2 vs 34.0±15.4 ml/m2, p<0.001), 3D-telediastolic LA volume (89.5±27.7 vs 66.8 ±31.9 ml/m2, p=0.002), 3D-telesistolic LA volume (43.6±15.3 vs 25.3±17.4 ml/m2, p <0.001), lower rates of LA ejection fraction (50 ±14.6 vs 62.7±11.8, p=0.001) and LA strain in reservoir (22.0±8.6 vs 30.4±10.5, p<0.001) and contraction (10.5±8.18 vs 17.1±7.5, p<0.001). After multivariable regression analysis (age, HTA and CHASDS2VASC) all the differences remained significative. High-burden nsAT/AE and NSR patients presented significant differences in LA index volume (33.4±12.4 vs 27.3±11.8 ml/m2, p=0.043) and LA strain in reservoir (26.6±12.5) vs 31.0±10.1, p=0.034) that disappeared after multivariate regression analysis. There were no significant differences in ischemic recurrence or mortality between the three groups. Conclusions In patients with cryptogenic stroke, we registered a high rate of AF and high-burden nsAT/AE. AF patients showed notable alterations in LA volume, LA function and reservoir and contraction strain, while patients with high-burden nsAT/AE showed less structural alteration in echocardiography without difference in stroke recurrence among groups.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

First pass effect in patients undergoing endovascular treatment for posterior circulation acute ischemic stroke

ObjectiveThis study aims to investigate the impact of first pass effect (FPE) on outcomes in the posterior circulation acute ischemic stroke (PC-AIS) and the independent predictors of FPE. MethodsThis was a multicenter, retrospective study. PC-AIS patients who underwent endovascular treatment were reviewed. The cohort achieving complete or nearly complete reperfusion (defined as expanded treatment in cerebralischemia [eTICI] ≥ 2c) was categorized into the FPE and multiple pass effect (MPE) groups. FPE was defined as achieving eTICI ≥ 2c with a single pass and without the use of rescue therapy. Modified FPE (mFPE) was defined as meeting the criteria for FPE but with eTICI ≥ 2b. The association of FPE with 90-day clinical outcomes and predictors for FPE were both investigated. ResultsThe study included a total of 328 patients, with 69 patients (21 %) in the FPE group. For primary outcome, FPE had a significant higher favorable outcome (mRS ≤ 3) rate than MPE (65.2 % vs. 44.8 %, p = 0.003). Similar outcomes were observed in the mFPE. Furthermore, FPE was significantly associated with favorable outcome (adjusted OR 2.23, 95 % CI 1.06-4.73, p = 0.036). Positive predictors for FPE included occlusion in the distal basilar artery, the first-line aspiration or combination, and cardioembolic etiology. Negative predictors for FPE included hypertension and general anesthesia. ConclusionFor PC-AIS patients due to large or medium vessel occlusion, FPE is associated with favorable clinical outcomes. The first-line techniques of aspiration or combination, as well as avoiding general anesthesia, contribute to a better realization of FPE.

Abstract WP277: Stroke Etiology in Young Adults With Substance Abuse

Introduction: Recent public health trends suggest increasing rates of substance abuse among young people. Substance use has been associated with an increased risk of stroke, and specifically, cocaine use is known to more likely cause lacunar and cardioembolic strokes. However, less is known about the stroke etiology with other substances. Methods: We conducted a retrospective review of stroke patients between the ages of 18 to 50 years presenting to our Young Stroke Center between April 2022 through August 2023. For each case, data including basic demographics and medical history were collected, and stroke etiology was determined by a vascular neurologist. Patients with substance use at the time of stroke were compared to all non-substance use related stroke and analyzed with respect to TOAST stroke etiology. Substance use was defined as use of opioids, cocaine, marijuana, or alcohol abuse. Analysis was performed with logistic regression adjusting for age, sex, and race. Results: Of 187 patients in the registry, 25 patients had substance use at time of stroke compared with 162 patients with non-substance use related stroke. There were 10 marijuana, 4 opioid, 0 cocaine, 3 alcohol abuse and 8 polysubstance use (including 3 cocaine) cases. There were no significant differences in age at time of stroke (36.9 ± 7.1 vs. 38.8 ± 8.2 years) and race (50.0% vs. 53.4% Black) between substance use and non-substance use related stroke groups, respectively. There was a significantly higher proportion of males with substance use (62.5% vs. 31.9% male; OR [95% CI]: 4.0 [1.6-10.0]). In the substance use group, a higher proportion had cardioembolic stroke etiology (20.8% vs. 9.2%; OR [95% CI]: 4.1 [1.2-14.0]); however, there was no significant difference with respect to the other TOAST stroke etiologies. In patients with active substance use and cardioembolic stroke etiology, heart failure with reduced ejection fraction and atrial fibrillation were the etiologies found. Conclusion: Our findings indicate that among young individuals with active substance use at the time of their stroke, cardioembolic etiology appears to be more likely than in young stroke patients without substance use. This underscores the need for comprehensive cardiac evaluation in this population.

Abstract WP270: Clonal Hematopoiesis of Indeterminate Potential (CHIP): Relationship With Ischemic Stroke Etiology

Clonal Hematopoiesis of Indeterminate Potential (CHIP) is defined by the presence of somatic mutations in peripheral blood cells without evidence of a hematological neoplasm. It has recently been associated with cardiovascular disease and stroke. The objective of our study is to evaluate the relationship of CHIP with the etiology of the ischemic stroke and how its measurement could contribute to the study of stroke causes. Material and Methods: Prospective observational study of consecutive patients who suffered an ischemic stroke between September 2021 and August 2022. After complete work-up, patients were classified as cardioembolic (CE), atherothrombotic (AT) and cryptogenic (CRIP) stroke; those who presented a double mechanism, incomplete study or were affected by an active neoplasia were excluded from the study. During hospital admission, 13 genes related to CHIP were analyzed, through targeted next generation sequencing. A variant allele fraction of &gt;2% was considered positive. Results: Samples from 78 patients (50% women, mean age 73.5 years) were analyzed and etiologically classified as: 37 CE (47.5%), 33 AT (42.3%) and 8 CRIP (10.3 %). Twenty-one patients had CHIP (31.3%), of which the predominating mutations were: DNMT3A (47.6%), TET2 (28.5%) and SFRS3 (14.2%). Patients diagnosed with CE stroke had a higher frequency of CHIP (p=0.046): CE 14/37 (37.8%) vs. AT 6/33 (18.2%) vs. CRIP 1/8 (12.5%); specifically of the TET2 mutation (p=0.015): CE 6/37 (16.2%) vs. AT 0/33 (0%) vs. CRIP 0/8 (0%). In the multivariate analysis, the TET2 mutation was associated with CE etiology after adjusting by age, coronary artery disease, and classic cardiovascular risk factors (OR 8.1; CI 1.35-48.47; p=0.012). Conclusions: CHIP is frequently found in patients with ischemic stroke. The presence of the TET2 mutation is associated with CE stroke and could constitute a new risk factor and contribute to a more accurate etiological stroke diagnosis.

Abstract TMP104: Timing of Recurrence After Ischemic Stroke by Subtype: A Population-Based Study

Introduction: Prior work suggests stroke recurrence timing may vary by subtype, with large vessel disease being associated with earlier recurrence; however, these studies were conducted prior to the current era of secondary stroke prevention strategies. We examined whether the timing of recurrence after ischemic stroke varied by subtype in a large population-based study. Methods: In 2015, we identified all acute ischemic stroke events from hospitals in the Greater Cincinnati and Northern Kentucky area. Events in the last 6 months of 2014 were oversampled for black patients. Trained nurses extracted clinical data, and stroke specialists subtyped and adjudicated cases. We tracked events for 3 years, considering only ischemic strokes after day 14 as a recurrence. To assess recurrence timing variations, we stratified strokes by subtype and analyzed their restricted mean survival times (RMST) at 1, 3, 12, 24, and 36 months. RMST is the area under the survival curve up to a specific follow up point, denoting the average event-free time during that interval. Results: Of 2577 patients with index stroke, 332 recurrent strokes were seen over the ensuing 3 years. Half of the recurrences occurred within 8 months from the index event. At 12 months, large vessel (LV), undetermined, and other identified cause showed a statistically significant smaller RMST compared to small vessel (SV). This difference was nonsignificant at later time points, suggesting later recurrence for SV. There were no statistically significant differences in RMST between cardioembolic, LV, undetermined, and other identified at any time point. Conclusions: Recurrence after initial SV stroke was less likely to occur in the first year when compared to LV, undetermined etiology, or other identified causes of stroke. There was no evidence of difference in recurrence timing between cardioembolic, LV, other identified, and undetermined etiology.

Cerebral small vessel disease and stroke: Linked by stroke aetiology, but not stroke lesion location or size

BackgroundCerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. MethodsIn a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. ResultsWith increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. ConclusionsIn patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

Exploring the Chagas Disease-Stroke “Connection”: Findings from a Large Multicenter Study

Introduction: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. Methods: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. Results: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia, and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific electrocardiography abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81 fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR: 0.98, 95% confidence interval [CI]: 0.970–0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR: 0.221, 95% CI 0.104–0.472), highlighting the importance of accurate etiological classification. Conversely, female gender (OR: 1.83, 95% CI: 1.039–3.249) emerged as a significant risk factor for stroke recurrence. Conclusion: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.

Left atrial reservoir strain is a superior discriminator of cardioembolism in ischaemic stroke.

Echocardiographic measures of left heart size and function have long been associated with cardioembolic mechanisms of stroke development, however, the diagnostic performance and comparison of measures of atrial function in this context has not been well studied. We sought to evaluate the diagnostic performance of left atrial reservoir strain (LASr) in identification of cardioembolism in the ischaemic stroke population relative to traditional measures of left heart size and function. Consecutive patients admitted to our institution with ischaemic stroke or transient ischaemic attack were recruited and underwent comprehensive transthoracic echocardiography. Strokes were classified by aetiology with comparison undertaken between cardioembolic and non-cardioembolic types. Four hundred and eighteen consecutive stroke patients with a cardioembolic (n = 229) or non-cardioembolic (n = 189) stroke aetiology were analysed. LASr was impaired in cardioembolic compared with non-cardioembolic strokes (16.7 ± 8.2% vs. 26.0 ± 5.5%, P < 0.01) and provided greatest discrimination [area under the curve (AUC) 0.813, 95%CI 0.773-0.858] in differentiating stroke subtypes when compared with LVEF (AUC difference 0.150, P < 0.01), LAVI (AUC difference 0.083, P < 0.01), and E/e' (AUC difference 0.163, P < 0.01). Inclusion of LASr in a model with conventional left heart echocardiographic factors improved model performance with a net reclassification improvement of 1.083 (95%CI 0.945-1.220, P < 0.01). Further, a proposed user-defined model-based clinical algorithm with LASr demonstrated improved diagnostic accuracy of the identification of cardioembolic stroke subtypes which was best appreciated in patients without atrial fibrillation. LASr may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate cardioembolic from non-cardioembolic stroke mechanisms, in particular amongst those without comorbid atrial fibrillation.

White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy

BackgroundLymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS. MethodsAIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots. Martius Scarlet Blue stain was used to identify the main histological components of the clots. Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns. The cellular and histological components were quantified using Orbit Image Analysis software. ResultsAT clots were larger, with more red blood cells and fewer WBCs than CE clots. AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies. Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots. There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots. ConclusionThe difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation.

Clonal Hematopoiesis of Indeterminate Potential (CHIP) Related to the Etiology of Ischemic Stroke

Introduction: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with cardiovascular disease, including acute myocardial infarction and ischemic stroke, due to immune system dysregulation leading to increased atherosclerotic plaque formation and inflammation. Approximately 25-40% of ischemic strokes have an unknown cause even after a comprehensive etiological study and are eventually categorized as cryptogenic strokes. Our hypothesis is that the presence of CHIP could represent a biomarker for atherosclerotic or cardioembolic ischemic stroke and help to clarify the origin of cryptogenic strokes. Therefore, the objective of this study was to analyze the prevalence of CHIP in patients with different subtypes of ischemic stroke and its prognostic impact on cardiovascular risk. Methods: This prospective observational study included consecutive patients over 60 years of age with no prior history of neoplasia or cytotoxic treatment, who experienced embolic ischemic stroke between September 2021 and August 2022. Ischemic strokes were classified into cardioembolic (CE), atherothrombotic (AT) or cryptogenic (CRYP) etiologies after performing a systematic etiological study. During the stroke admission, peripheral blood samples were obtained in order to analyze the 13 genes most frequently associated with CHIP ( DNMT3A, TET2, ASXL1, JAK2, PPM1D, TP53, SF3B1, GNB1, SRSF2, CHEK2, CBL, GNAS, NRAS) through targeted next generation sequencing. Libraries were prepared using the KAPA HyperPlus capture chemistry (Roche) and were sequenced on a MiSeq platform (Illumina) following a 2x150bp paired-end read standard protocol, allowing the detection of variants with a variant allelic frequency (VAF) of ≥1%. The analysis was conducted using an in-house developed pipeline. Patients with one or more mutations in these genes with a VAF ≥2% were considered CHIP carriers. Cardiovascular risk factors including: hypertension, diabetes mellitus, dyslipidemia, smoking and obesity, were also analyzed. Results: Seventy-eight patients with stroke were included (50% female, median age 72 years (range: 59-90). Ischemic strokes were classified etiologically as: 36 CE (46.2%), 34 AT (43.6%) and 8 CRYP (10.3%) (Table 1). CHIP was detected in 21/78 (31.3%) patients, with the following gene mutation frequencies among CHIP carriers: DNMT3A (47.6%), TET2 (28.5%), SRSF2 (14.2%), PPM1D (9.5%), ASXL1 (4.8%), CBL (4.8%), CHEK2 (4.8%) and JAK2 (4.8%). The median VAF detected was 4.85% (range: 2.1%-43.7%), and 23.8% (5/21) of cases presented more than one mutation. The incidence of CHIP varied according to stroke etiology: CE etiology: 38.9% (14/36); AT etiology: 17.6% (6/34) and CRYP etiology: 12.5% (1/8) (p=0.046) (Figure 1). Moreover, only CE strokes showed mutations in TET2 (16.7% (6/36)) compared to AT (0/34) and CRYP (0/8) (p=0.015). No significant differences were observed in the blood counts (Hb, MCV, RDW, neutrophil count, monocytes, platelets or PCR) between stroke patients with CHIP and non-CHIP (Table 1). Finally, in the multivariate analysis, TET2 mutations were associated with CE stroke independently of age, coronary artery disease and classic cardiovascular risk factors (OR 8.1; Cl: 1.35-48.47; p=0.012). Conclusions: Our findings identify that CHIP is common in patients with ischemic strokes, especially in those of cardioembolic etiology, with TET2 being the most frequently mutated gene. The presence of CHIP TET2 could represent a novel cardiovascular risk factor, contributing to a more precise etiological distinction between the different etiologies of ischemic stroke. Funding source: this project is supported by health research fund of Carlos III health institute. FIS PI20/00881

Abstract 248: Structural Analysis of Aspiration Catheters and Procedural Outcomes: An Analysis of the SVIN Registry

Introduction Rapid expansion of mechanical thrombectomy and swift manufacturing development has translated into significant evolution of large bore catheter technology. The objective of this study was to evaluate the association among diverse structural components of large bore aspiration catheters on procedural performance. Methods Retrospective analysis of a prospectively maintained mechanical thrombectomy consortium (SVIN Registry) treated with stand‐alone contact aspiration for the first pass in the MCA M1 or intracranial ICA occlusions from 2012‐2021. Catheters were stratified based on construction materials, tip technology, catheter sizing, and catheter lining. Factors associated with first pass effect (FPE ‐ first‐pass eTICI2c‐3 reperfusion) as well as speed of clot engagement were analyzed. Results We identified 983 patients with proximal occlusion and aspiration as the first pass technique. FPE was observed in 34% and associated with age (OR:1.016;95%CI:1.006‐1.027), cardioembolic stroke etiology (OR:1.685;95%CI:1.77 ‐2.41), MCA M1(OR:2.737;95%CI:1.091 ‐1.867), non‐general anesthesia (OR:0.546;95%CI:0.389 ‐0.767), as well as with 0.070” (OR:2.038;95%CI:1.099 ‐3.779) and 0.088” (OR:3.899;95%CI:1.582 ‐9.606) distal catheter inner diameter in the adjusted analysis. Median time from arterial access to clot contact was 17 minutes with faster times observed in younger patients (OR:0.986;95%CI:0.975 ‐0.996) as well as with the use of aspiration catheters with shorter length of distal outer hydrophilic coating (18‐30cm) on multivariable regression (OR:0.303; 95%CI:0.113‐0.816). Conclusion Larger aspiration catheter distal inner diameter was associated with higher rates of FPE. Aspiration catheters with reduced distal tip hydrophilic coating were associated with faster arterial access to clot contact time.

Yield of Cardiac Investigations in Patients Presenting with Acute Ischaemic Stroke: A single tertiary centre experience.

Strokes are a major cause of morbidity and mortality. This study aimed to evaluate the effectiveness of routine cardiac investigations in identifying a cardioembolic aetiology for ischaemic strokes. This retrospective study involved patients who presented with a stroke to the Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2019. A total of 183 patients (mean age = 66.2 ± 13.5 years), the majority of which were male (n = 109, 59.6%), were included. The common risk factors included hypertension (74.9%), diabetes (61.7%) and hyperlipidaemia (54.6%). The middle cerebral artery was the most common artery affected, in 44 patients (24.0%). On admission, 14 (7.6%) patients were in atrial fibrillation (AF), while the rest were in sinus rhythm. The 24-hour electrocardiogram (ECG) Holter monitoring revealed no abnormalities in 135 patients. AF was observed in 15 (8.1%) patients (inclusive of the 14 who had AF on resting ECG). Furthermore, 32 (17.4%) patients had evidence of non-sustained atrial arrhythmia, and nine (4.9%) had non-sustained ventricular tachycardia. Frequent supraventricular ectopics (>30/hour) was noted on 30 patients (16.3%), while five (2.7%) patients had a high ventricular ectopic burden (>10% burden). No significant abnormalities were noted in the echocardiograms of the patients; however, 10 out of 132 (7.5%) patients presented a positive bubble echo. Enlarged left atria were found in 24 (13.1%) patients. The overall diagnostic yield of the abnormalities from routine cardiac testing for patients with stroke appears to be low. Targeted screening of patients with cryptogenic stroke, as suggested by newer guidelines, is recommended.

Outcomes of recurrent stroke in patients with atrial fibrillation according to presumed etiology.

Atrial fibrillation (AF) is a potent risk factor for stroke. The presence of competing etiologies can modify disease outcomes and demand different treatment strategies. The primary purpose of the study was to examine the differences in outcomes for patients with AF admitted with a recurrent stroke, stratified according to the presumed etiology of the stroke. We analyzed AF patients admitted for a recurrent ischemic stroke in an academic comprehensive stroke center. Recurrent strokes were categorized as "Cardioembolic", meaning AF without any competing mechanism, versus "Undetermined" etiology due to competing mechanisms. We used logistic regression to test the association between recurrent stroke etiology and favorable outcome (discharge home), after accounting for important covariates. We included 230 patients, with a mean age 76.9 (SD ± 11.3), 52.2% male, median National Institute of Health Stroke Scale (NIHSS) score of 7 (IQR 2-16). Patients with cardioembolic stroke (65.2%) had higher median NIHSS 8.5 (3-18) versus 3 (1-8) and were more likely to be treated with reperfusion therapies. The favorable outcome was reached by 64 patients (27.8%), and in-hospital mortality was 15.2% overall. After adjustment, there was no difference in outcome between patients with cardioembolic versus undetermined stroke etiology (odds ratio for discharge home: 1.41; 95% CI: 0.65-3.15). In this single-center sample of AF patients with history of stroke, there was no difference in discharge outcomes between those with cardioembolic and those with undetermined stroke etiology. This question warrants examination in larger samples to better understand the importance of the stroke mechanism and secondary prophylaxis.

Temporal trends in results of endovascular treatment of anterior intracranial large cerebral vessel occlusion: A 7-year study.

Technical improvements in devices, changes in angiographic grading scales and various confounding factors have made difficult the detection of the temporal evolution of angiographic and clinical results after endovascular treatment (EVT) for acute ischemic Stroke (AIS). We analyzed this evolution in time using the Endovascular Treatment in Ischemic Stroke (ETIS) registry. We analyzed the efficacy outcomes of EVT performed from January 2015 to January 2022, and modelized the temporal trends using mixed logistic regression models, further adjusted for age, intravenous thrombolysis prior to EVT, general anesthesia, occlusion site, balloon catheter use and the type of first-line EVT strategy. We assessed heterogeneity in temporal trends according to occlusion site, balloon catheter use, cardio embolic etiology, age (<80 years vs ⩾80 years) and first-line EVT strategy. Among 6104 patients treated from 2015 to 2021, the rates of successful reperfusion (71.1%-89.6%) and of complete first pass effect (FPE) (4.6%-28.9%) increase, whereas the rates of patients with >3 EVT device passes (43.1%-17.5%) and favorable outcome (35.8%-28.9%) decrease significantly over time. A significant heterogeneity in temporal trends in successful reperfusion according to the first-line EVT strategy was found (p-het = 0.018). The temporal trend of increasing successful reperfusion rate was only significant in patients treated with contact aspiration in first-line (adjusted overall effect p = 0.010). In this 7-year-old large registry of ischemic stroke cases treated with EVT, we observed a significant increase with time in the rate of recanalization whereas there was a tendency toward a decrease in the rate of favorable outcome over the same period.